Impact of hereditary multigene panel testing for cancer survivors.

2016 ◽  
Vol 34 (3_suppl) ◽  
pp. 261-261
Author(s):  
Nimmi S. Kapoor ◽  
Jennifer Swisher ◽  
Rachel E. McFarland ◽  
Mychael Patrick ◽  
Lisa D. Curcio
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Survivors ◽  
Gene Mutation ◽  
Gene Panel ◽  
Personal History ◽  
Panel Testing ◽  
Pathogenic Mutations ◽  
Gene Panel Testing ◽  
History Of

261 Background: Recently, genetic testing for hereditary cancer syndromes has seen numerous advances in testing spectrum, capability, and efficiency. This may have important implications for cancer survivors and their families. The purpose of this study is to evaluate the impact of reflex genetic testing with newer multi-gene panels on patients with prior negative BRCA1/2 tests. Methods: Data was collected retrospectively from patients who underwent multi-gene panel testing at one of three sites from a single institution between 8/2013-6/2015. Those with a personal history of breast or ovarian cancer and a prior negative BRCA1/2 test were included. Results: Of 914 patients who underwent multi-gene panel tests, 187 met study inclusion criteria. Ten patients (5.3%) were found to carry 11 pathogenic mutations, including 6 patients with mutations in CHEK2, 2 patients with mutations in PTEN, and 1 patient each with mutations in the following genes: BARD1, NF1, and RAD51C. One patient had two pathogenic mutations identified—CHEK2 and BARD1. Of 10 patients with mutations, 9 had a personal history of breast cancer diagnosed at a median age of 43 (range 35-52) and 1 had ovarian cancer diagnosed at age 65. A majority of mutation carriers underwent panel testing years after their cancer diagnosis (median 6 years, range 0.5-32 years) and none with delayed testing had undergone prophylactic contralateral mastectomy prior to the discovery of their gene mutation. All patients with mutations had a family history of at least one cancer, with most having a variety of cancer diagnoses in multiple relatives. Positive panel testing results altered clinical management in most patients, including addition of breast MRI, colonoscopy, or thyroid ultrasound depending on the gene mutation. After discovery of a PTEN mutation 19 years after her initial cancer treatment, one woman underwent bilateral prophylactic mastectomy and was found to have occult ductal carcinoma in situ. Conclusions: Cancer survivorship must incorporate advances in technology that may be beneficial even years after treatment has ended. Multi-gene panel testing can be applied in survivorship settings as a useful tool to guide screening recommendations.

scholarly journals Extended gene panel testing in lobular breast cancer

2021 ◽  
Author(s):  
Elke M. van Veen ◽  
D. Gareth Evans ◽  
Elaine F. Harkness ◽  
Helen J. Byers ◽  
Jamie M. Ellingford ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Detection Rate ◽  
Gene Panel ◽  
Lobular Breast Cancer ◽  
Germline Variants ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
Increased Risk

AbstractPurpose: Lobular breast cancer (LBC) accounts for ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC. Methods: 302 women with LBC and 1567 without breast cancer were tested for BRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative for BRCA1/2 PGVs underwent extended screening, including: ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.Results: 35 PGVs were identified in the group with LBC, of which 22 were in BRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4), CDH1(1), CHEK2(1), PALB2(2) and TP53(2)). Overall, PGVs in three genes conferred a significant increased risk for LBC. Odds ratios (ORs) were: BRCA1: OR = 13.17 (95%CI 2.83–66.38; P = 0.0017), BRCA2: OR = 10.33 (95%CI 4.58–23.95; P < 0.0001); and ATM: OR = 8.01 (95%CI 2.52–29.92; P = 0.0053). We did not detect an increased risk of LBC for PALB2, CDH1 or CHEK2. Conclusion: The overall PGV detection rate was 11.59%, with similar rates of BRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants in ATM with LBC.

scholarly journals MS3-1 IMPLEMENTATION OF GENE PANEL TESTING USING NEXT-GENERATION SEQUENCING

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii3-ii3
Author(s):  
Kazuko Sakai
Keyword(s):  
Cancer Treatment ◽  
Gene Mutation ◽  
Diagnostic Testing ◽  
Gene Panel ◽  
Panel Testing ◽  
Formalin Fixed Paraffin ◽  
Gene Panel Testing ◽  
Companion Diagnostic ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Abstract The advance of next-generation sequencers (NGS) has dramatically improved the performance of genomic analysis of clinical samples in cancer precision medicine. The practical use of gene panel testing for clinical applications has begun in Japan. At present, “OncomineTM Dx Target Test” is listed as a companion diagnostic system using NGS, and “FoundationOne CDx Cancer Genomic Profile” and “OncoGuide™ NCC Oncopanel System” are listed as gene panel testing under insurance coverage. Formalin-fixed paraffin-embedded specimen have been routinely used for molecular diagnosis testing, therefore quality control such as formalin fixation time and tumor contents is important to ensure validity of diagnostic results. In this presentation, the issue to obtain evaluable results of gene panel testing using formalin-fixed paraffin-embedded specimen will be discussed. Due to evolution of detection technologies, we can detect gene mutation with high sensitivity. Detection of gene mutation in circulating tumor DNA is feasible approach for diagnostic testing in cancer treatment. Liquid biopsy has been approved as a companion diagnostic testing to detect EGFR mutations in NSCLC. Examples of the clinical utility of plasma testing in cancer treatment will be presented.

Clinical impact of multi-gene panel testing for hereditary breast and ovarian cancer risk assessment.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 1513-1513
Author(s):  
Leif W. Ellisen ◽  
Allison W. Kurian ◽  
Andrea J Desmond ◽  
Meredith Mills ◽  
Stephen E Lincoln ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Assessment ◽  
Cancer Risk ◽  
Clinical Impact ◽  
Gene Panel ◽  
Cancer Risk Assessment ◽  
Ovarian Cancer Risk ◽  
Breast And Ovarian Cancer ◽  
Panel Testing ◽  
Gene Panel Testing

Benefits and safety of multigene panel testing in patients at risk for hereditary breast cancer.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 16-16
Author(s):  
Nimmi S. Kapoor ◽  
Lisa D. Curcio ◽  
Carlee A. Blakemore ◽  
Amy K. Bremner ◽  
Rachel E. McFarland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Genetic Testing ◽  
Hereditary Breast Cancer ◽  
Diagnostic Yield ◽  
Gene Panel ◽  
Panel Testing ◽  
Gene Testing ◽  
Gene Panel Testing ◽  
Patients At Risk

16 Background: Recently introduced multi-gene panel testing including BRCA1 and BRCA2 genes (BRCA1/2) for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study is to evaluate rates of pathogenic BRCA1/2mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multi-gene testing. Methods: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2testing only (limited group, n = 629) to those who underwent multi-gene testing with 5-43 cancer-related genes (panel group, n = 337). Results: Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0% vs 3.6%, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5% vs 3.3%, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9% (n = 13) had non-BRCA pathogenic mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified. Conclusions: Multi-gene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly due to non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from upfront, more efficient, multi-gene panel testing.

Expanded yield of multiplex panel testing in fully accrued prospective trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1525-1525
Author(s):  
Gregory Idos ◽  
Allison W. Kurian ◽  
Charite Nicolette Ricker ◽  
Duveen Sturgeon ◽  
Julie Culver ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Clinical Utility ◽  
Diagnostic Yield ◽  
Pathogenic Mutation ◽  
Gene Panel ◽  
Cancer Risk Assessment ◽  
Panel Testing ◽  
Gene Panel Testing

1525 Background: Genetic testing is a powerful tool for stratifying cancer risk. Multiplex gene panel (MGP) testing allows simultaneous analysis of multiple high- and moderate- penetrance genes. However, the diagnostic yield and clinical utility of panels remain to be further delineated. Methods: A report of a fully accrued trial (N = 2000) of patients undergoing cancer-risk assessment. Patients were enrolled in a multicenter prospective cohort study where diagnostic yield and off-target mutation detection was evaluated of a 25 gene MGP comprised of APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Patients were enrolled if they met standard testing guidelines or were predicted to have a ≥2.5% mutation probability by validated models. Differential diagnoses (DDx) were generated after expert clinical genetics assessment, formulating up to 8 inherited cancer syndromes ranked by estimated likelihood. Results: 1998/2000 patients had reported MGP test results. Women constituted 81% of the sample, and 40% were Hispanic; 241 tested positive for at least 1 pathogenic mutation (12.1%) and 689 (34.5%) patients carried at least 1 variant of uncertain significance. The most frequently identified mutations were in BRCA1 (17%, n = 41), BRCA2 (15%, n = 36), APC (8%, n = 19), CHEK2 (7%, n = 17), ATM (7%, n = 16). 39 patients (16%) had at least 1 pathogenic mutation in a mismatch repair (MMR) gene ( MLH1, n = 10; MSH2, n = 10; MSH6, n = 8; PMS2, n = 11). 43 individuals (18%) had MUTYH mutations – 41 were monoallelic. Among 19 patients who had mutations in APC – 16 were APC I1307K. Only 65% (n = 159) of PV results were included in the DDx, with 35% (n = 86) of mutations not clinically suspected. Conclusions: In a diverse cohort, multiplex panel use increased genetic testing yield substantially: 35% carried pathogenic mutations in unsuspected genes, suggesting a significant contribution of expanded multiplex testing to clinical cancer risk assessment. The identification of off-target mutations broadens our understanding of cancer risk and genotype-phenotype correlations. Follow-up is ongoing to assess the clinical utility of multiplex gene panel testing. Clinical trial information: NCT02324062.

Performance of mutation risk prediction models in a racially diverse multi-gene panel testing cohort.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1523-1523
Author(s):  
Gregory Idos ◽  
Katherine G Roth ◽  
Leah Naghi ◽  
Charite Nicolette Ricker ◽  
Julie Culver ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Genetic Testing ◽  
Prediction Models ◽  
Brca2 Mutation ◽  
Pathogenic Mutation ◽  
Gene Panel ◽  
Panel Testing ◽  
Gene Panel Testing ◽  
Brca1 Brca2 ◽  
Racial Ethnic

1523 Background: Mutation carrier prediction models are clinically useful tools for identifying candidates for genetic counseling and testing. Consensus guidelines recommend germline genetic testing for those with a carrier probability (CP) of approximately 5% or higher. However, prediction models may perform less well among racial/ethnic minorities. Our hypothesis is that pathogenic mutations (PM) are identifiable in a clinically meaningful fraction of racially/ethnically diverse patients with a CP of < 5%. Methods: We conducted a multicenter prospective clinical trial of patients undergoing cancer-risk assessment using a 25 gene panel, which include APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Patients were recruited from August 2014 to November 2016 at three centers. Patients were enrolled if they met standard clinical criteria for genetic testing or were predicted to have a ≥2.5% probability of inherited cancer susceptibility using validated prediction models. We evaluated the CP of patients with a PM in BRCA1, BRCA2, and/or a mismatch repair (MMR) gene using the following models: (1) BRCApro, (2) MMRpro and (3) PREMM1,2,6. Results: Of 2000 patients enrolled in this cohort, 80.6% are female (n = 1612). Regarding race/ethnicity, the cohort is 40.1% Non-Hispanic White (n = 802), 37.4% Hispanic (n = 748), 11.5% Asian (n = 230), 3.9% Black (n = 78), and 7.1% Other (n = 142). Among 241 (12.1%) patients who tested positive for a pathogenic mutation, 76 (31.5%) patients had a BRCA1 or BRCA2 mutation. Of those, 52 (68.4%) patients had a BRCApro CP of < 5%. Thirty-eight (15.8%) patients had a pathogenic mutation in an MMR gene: 19 (50.0%) had an MMRpro CP of < 5%, while 13 (34.2%) had a PREMM1,2,6 CP of < 5%. The racial/ethnic distribution of BRCA1/2 or MMR mutation carriers is similar to that of the whole cohort. Conclusions: In a diverse cohort of patients undergoing 25-gene multiple-gene panel testing, half or more carriers of BRCA1/2 or MMR mutations had a CP of < 5%, the consensus guideline-recommended cutoff for genetic testing. These results support a lower threshold for genetic testing guidelines. Clinical trial information: NCT02324062.

Characteristics of probands with mutations predisposing to gynecologic cancers enrolled in a facilitated cascade testing protocol.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13682-e13682
Author(s):  
Kristina Hwang ◽  
Katherine Baumann ◽  
Allison Brodsky ◽  
Kathleen Lutz ◽  
Deanna Gerber ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Diagnosis ◽  
Genetic Mutation ◽  
Personal History ◽  
Gynecologic Cancers ◽  
Cascade Testing ◽  
Pathogenic Mutations ◽  
History Of ◽  
Mutation Identification ◽  
History Of Cancer

e13682 Background: We sought to evaluate the feasibility of obtaining genetic testing (GT) for first- or second-degree (1°, 2°) family members of a proband known to have actionable germline mutation associated with endometrial and/or ovarian cancer through a coordinated referral system. Here we characterize the initial probands and discuss the time frame of their enrollment in facilitated cascade testing (CT). Methods: Patients with pathogenic mutations associated with gynecologic cancers were determined from cancer genetics and gynecologic oncology clinics. Consenting patients completed a RedCap survey on personal cancer history and history of GT. They were then asked to contact 1° and/or 2° relatives regarding their GT results. Relatives were advised to contact our team. Relatives who consented to the study were referred for GT and contacted for follow up to ascertain whether they received GT and/or took action to reduce cancer risk. Results: From 3/2019- 1/2020, this study has accrued 39 probands. The median age was 39 years (range: 25-68). The most commonly expressed gene mutations were BRCA1 or BRCA2 (87.18%, n=34). Other mutations included BRIP1, MLH1, MSH2, MSH6, and PMS2. The majority (62%) of probands had no personal history of cancer. Among those who had a history of cancer (n=15), 80% had breast and/or ovarian cancer, and 80% reported their genetic mutation was discovered at or after the time of their cancer diagnosis. Median age at time of enrollment in CT was 49 years (range: 29-66) for patients with a history of cancer and 32 years (range: 25- 68) for those without, (p=0.009). Among all probands, the median time between mutation identification and enrollment in CT was 2 years (range=0 to 11). There was no significant difference in time between mutation identification and enrollment in CT when comparing those with and without cancer histories (p=0.5). Conclusions: These results suggest that patients with pathogenic mutations predisposing to gynecologic cancer are willing to undergo CT even if they have no personal history of cancer. Patients with a history of cancer tend to be older at time of enrollment in CT, likely because most discover their genetic mutation at or after the time of cancer diagnosis. With an average of 2 years elapsed between time of mutation identification and enrollment in CT, there is need for expansion of CT accessibility. Increased education and awareness among patients and providers in identifying those who may benefit from CT, screening, and risk reducing surgery to prevent cancer is needed.

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